Solution structure and internal motion of a bioactive peptide derived from nerve growth factor.

The conformation and internal dynamics of a bioactive cyclic peptide, N-acetyl-YCTDEKQCY, derived from the C-D loop of beta-nerve growth factor (beta-NGF) were analyzed by solution NMR spectroscopy. NMR experimental data were used to calculate an ensemble of peptide structures. All of the structures had a beta-turn at residues Asp4-Gln7 but could be divided into two families according the presence or absence of a hydrogen bond at Gln7. Comparison of the calculated structures with the corresponding C-D loops from the x-ray structures of the NGF revealed striking similarity. The orientation of Glu5, Lys6, and Gln7 side chains in the NGF mimetic was very similar to the C-D loop of NGF. These residues are known to participate in interactions with the TrkA receptor. Relaxation measurements of the peptidomimetic alpha-carbons at 13C natural abundance and calculated dynamic parameters suggest that the loop region of peptide is well structured but that residues Thr3, Asp4, Glu5, and Lys6 undergo slow conformational exchange. These results suggest that conformational similarity and possibly peptide dynamics are responsible for the bioactivity of the peptide.